Demographic variables shape longitudinal proteome signatures of peripheral nerve injury in mice

Our comprehensive proteomic analysis of mouse sciatic nerves following Spared Nerve Injury (SNI) reveals new dimensions of the molecular mechanisms underlying peripheral nerve injury, shaped by sex, developmental stage, and progression over time. Building on our previous work profiling naïve sciatic nerves (Xian et al., 2022), this study provides a uniquely longitudinal proteomic perspective on sciatic nerve injury, capturing both acute (7 to 14 days post SNI) and chronic (98 days post SNI) proteome changes. By integrating MEFISTO, a time-aware latent factor model, we uncovered intricate proteome dynamics and identified conserved patterns of reorganization. Notably, a robust sex-shared response emerged, reflecting sequential transitions: from early neuronal injury/repair and metabolic adjustments to late-stage structural and transcriptional remodeling alongside sterile inflammation. In addition, observed sex-biased differences in immune and neuronal function further refine our knowledge of divergent aspects of peripheral nerve injury. In summary, we provide an expansive resource, which advances our understanding how demographic variables shape longitudinal peripheral nerve plasticity, associated pathologies, and possibly regeneration. Importantly, our study highlights the opportunities of inclusive, temporally resolved experimental designs in preclinical research.